Recent studies of herpes simplex virus infections of the nervous system have largely defined the progression of the infection as it moves from a peripheral site of infection through the peripheral nerves via axoplasmic flow, to the sensory ganglia into the spinal cord and finally to the brain. This progression can be altered at the sensory ganglia where the virus can establish a latent infection in the neurons. This proposal is basically concerned with obtaining information to further our understanding of the pathogenesis and consequences of herpes simplex virus infections of the nervous system. Due to the greater control which can be exercised in a tissue culture environment, we plan to develop a tissue culture model of rat skin-rat dorsal root ganglia. Initial efforts will be devoted to characterizing the ultrastructural and electrophysiological aspects of this model. Next, these same parameters will be examined after MacIntyre virus infection of the cultures. Finally, we will determine the effects of various components of the rat's immune system (anti-viral antibody, complement, interferon, rat "T" and "B" lymphocytes, and macrophages) on the pathogenesis of the virus.